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Considerations for Certain Concomitant Medications in Patients with COVID-19

Last Updated: July 30, 2020

Summary Recommendations
Summary Recommendations

Angiotensin-Converting Enzyme (ACE) Inhibitors and Angiotensin Receptor Blockers (ARBs)

  • Persons with COVID-19 who are prescribed ACE inhibitors or ARBs for cardiovascular disease (or other indications) should continue these medications (AIII).
  • The COVID-19 Treatment Guidelines Panel (the Panel) recommends against the use of ACE inhibitors or ARBs for the treatment of COVID-19, except in a clinical trial (AIII).

Corticosteroids

For management of COVID-19

  • On the basis of the preliminary report from the Randomised Evaluation of COVID-19 Therapy (RECOVERY) trial, the Panel recommends using dexamethasone 6 mg per day for up to 10 days for the treatment of COVID-19 in patients who are mechanically ventilated (AI) and in patients who require supplemental oxygen but who are not mechanically ventilated (BI).
  • The Panel recommends against using dexamethasone for the treatment of COVID-19 in patients who do not require supplemental oxygen (AI).
  • If dexamethasone is not available, the Panel recommends using alternative glucocorticoids such as prednisone, methylprednisolone, or hydrocortisone (AIII).
  • See Corticosteroids for a detailed discussion of these recommendations.

For patients on chronic corticosteroids

  • Oral corticosteroid therapy that was used prior to COVID-19 diagnosis for another underlying condition (e.g., primary or secondary adrenal insufficiency, rheumatological diseases) should not be discontinued (AIII). On a case-by-case basis, supplemental or stress-dose steroids may be indicated (AIII).
  • Inhaled corticosteroids that are used daily for patients with asthma and chronic obstructive pulmonary disease for control of airway inflammation should not be discontinued in patients with COVID-19 (AIII).
Considerations in pregnancy
  • Given the potential benefit of decrease in maternal mortality and the low risk of fetal adverse effects for this short course of therapy, the Panel recommends using dexamethasone in pregnant women with COVID-19 who are mechanically ventilated (AIII) or who require supplemental oxygen but who are not mechanically ventilated (BIII).

HMG-CoA Reductase Inhibitors (Statins)

  • Persons with COVID-19 who are prescribed statin therapy for the treatment or prevention of cardiovascular disease should continue these medications (AIII).
  • The Panel recommends against the use of statins for the treatment of COVID-19, except in a clinical trial (AIII).

Nonsteroidal Anti-Inflammatory Drugs (NSAIDs)

  • Persons with COVID-19 who are taking NSAIDs for a comorbid condition should continue therapy as previously directed by their physician (AIII).
  • The Panel recommends that there be no difference in the use of antipyretic strategies (e.g., with acetaminophen or NSAIDs) between patients with or without COVID-19 (AIII).

Angiotensin-Converting Enzyme Inhibitors and Angiotensin Receptor Blockers

Recommendations

  • Persons with COVID-19 who are prescribed angiotensin-converting enzyme (ACE) inhibitors or angiotensin receptor blockers (ARBs) for cardiovascular disease (or other indications) should continue these medications (AIII).
  • The COVID-19 Treatment Guidelines Panel (the Panel) recommends against the use of ACE inhibitors or ARBs for the treatment of COVID-19, except in a clinical trial (AIII).

Angiotensin-converting enzyme 2 (ACE2) is the cell surface receptor for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). It has been hypothesized1 that the modulation of ACE2 associated with ACE inhibitors or ARBs could suppress or enhance SARS-CoV-2 replication.2 Investigations of the role of ARBs and recombinant human ACE2 in the treatment and prevention of SARS-CoV-2 infection are underway.3

Whether these medications are helpful, harmful, or neutral in the pathogenesis of SARS-CoV-2 infection is unclear. Currently, there is a lack of sufficient clinical evidence demonstrating that ACE inhibitors or ARBs have any impact on the susceptibility of individuals to SARS-CoV-2 or on the severity or outcomes of infection. The Panel's recommendation against the use of these medications for the treatment of COVID-19 is in accord with a joint statement of the American Heart Association, the Heart Failure Society of America, and the American College of Cardiology.3

Corticosteroids

It has been proposed that the anti-inflammatory effects of corticosteroids have a potential therapeutic role in suppressing cytokine-related lung injury in patients with COVID-19.4 Data reported for other respiratory infections have shown that systemic corticosteroids can affect the pathogenesis of these infections in various ways. In outbreaks of other novel coronavirus infections5,6 (i.e., Middle East respiratory syndrome [MERS] and SARS), corticosteroid therapy was associated with delayed virus clearance. In severe pneumonia caused by influenza, corticosteroid therapy may lead to worse clinical outcomes, including secondary bacterial infection and mortality.7

Preliminary clinical trial data from a large, randomized, open-label trial suggest that dexamethasone reduces mortality in hospitalized patients with COVID-19 who require mechanical ventilation or supplemental oxygen.8 The recommendations for using corticosteroids in patients with COVID-19 depend on the severity of illness. Before initiating dexamethasone, clinicians should review the patient’s medical history and assess the potential risks and benefits of administering corticosteroids to the patient.

For Management of COVID-19

Recommendations

  • On the basis of the preliminary report from the Randomised Evaluation of COVID-19 Therapy (RECOVERY) trial, the Panel recommends using dexamethasone 6 mg per day for up to 10 days for the treatment of COVID-19 in patients who are mechanically ventilated (AI) and in patients who require supplemental oxygen but who are not mechanically ventilated (BI).
  • The Panel recommends against using dexamethasone for the treatment of COVID-19 in patients who do not require supplemental oxygen (AI).
  • If dexamethasone is not available, the Panel recommends using alternative glucocorticoids such as prednisone, methylprednisolone, or hydrocortisone (AIII).

See Corticosteroids for a detailed discussion of these recommendations.

Patients on Chronic Systemic Corticosteroid Therapy

Patients with COVID-19 may also be receiving systemic corticosteroid therapy for a variety of underlying conditions.

Recommendation

  • Oral corticosteroid therapy that was used prior to COVID-19 diagnosis for another underlying condition (e.g., primary or secondary adrenal insufficiency, rheumatological diseases) should not be discontinued (AIII).9 On a case-by-case basis, supplemental or stress-dose steroids may be indicated (AIII).

Patients on Inhaled Corticosteroids

Recommendation

  • Inhaled corticosteroids that are used daily for patients with asthma and chronic obstructive pulmonary disease for control of airway inflammation should not be discontinued in patients with COVID-19 (AIII). No studies to date have investigated the relationship between inhaled corticosteroids in these settings and virus acquisition, severity of illness, or viral transmission.

Pregnancy Considerations

A short course of betamethasone and dexamethasone, which are corticosteroids known to cross the placenta, is routinely used to hasten fetal lung maturity and decrease the risk of neonatal respiratory distress syndrome in the premature infant with threatened delivery.10,11

  • Given the potential benefit of decrease in maternal mortality and the low risk of fetal adverse effects for this short course of therapy, the Panel recommends using dexamethasone in pregnant women with COVID-19 who are mechanically ventilated (AIII) or who require supplemental oxygen but who are not mechanically ventilated (BIII).

HMG-CoA Reductase Inhibitors (Statins)

Recommendations

  • Persons with COVID-19 who are prescribed statin therapy for the treatment or prevention of cardiovascular disease should continue these medications (AIII).
  • The Panel recommends against the use of statins for the treatment of COVID-19, except in a clinical trial (AIII).

HMG-CoA reductase inhibitors, or statins, affect ACE2 as part of their function in reducing endothelial dysfunction. It has been proposed that these agents have a potential role in managing patients with severe COVID-19.12 Observational studies have reported that statin therapy may reduce cardiovascular morbidity in patients admitted with other respiratory infections, such as influenza and bacterial pneumonia.

Nonsteroidal Anti-Inflammatory Drugs

Recommendations

  • Persons with COVID-19 who are taking nonsteroidal anti-inflammatory drugs (NSAIDs) for a comorbid condition should continue therapy as previously directed by their physician (AIII).
  • The Panel recommends that there be no difference in the use of antipyretic strategirs (e.g., with acetaminophen or NSAIDs) between patients with or without COVID-19 (AIII).

In mid-March 2020, news agencies promoted reports that anti-inflammatory drugs may worsen COVID-19. It has been proposed that NSAIDs such as ibuprofen can increase the expression of ACE21 and inhibit antibody production.13 Shortly after these reports, the Food and Drug Administration stated that there is no evidence linking the use of NSAIDs with worsening of COVID-19 and advised patients to use NSAIDs as directed.14

References

  1. Fang L, Karakiulakis G, Roth M. Are patients with hypertension and diabetes mellitus at increased risk for COVID-19 infection? Lancet Respir Med. 2020;8(4):e21. Available at: https://www.ncbi.nlm.nih.gov/pubmed/32171062.
  2. Patel AB, Verma A. COVID-19 and angiotensin-converting enzyme inhibitors and angiotensin receptor blockers: what is the evidence? JAMA. 2020. Available at: https://www.ncbi.nlm.nih.gov/pubmed/32208485.
  3. American College of Cardiology. HFSA/ACC/AHA statement addresses concerns re: using RAAS antagonists in COVID-19. 2020. Available at: https://www.acc.org/latest-in-cardiology/articles/2020/03/17/08/59/hfsa-acc-aha-statement-addresses-concerns-re-using-raas-antagonists-in-covid-19. Accessed July 16, 2020.
  4. Siddiqi HK, Mehra MR. COVID-19 illness in native and immunosuppressed states: a clinical-therapeutic staging proposal. J Heart Lung Transplant. 2020;39(5):405-407. Available at: https://www.ncbi.nlm.nih.gov/pubmed/32362390.
  5. Arabi YM, Mandourah Y, Al-Hameed F, et al. Corticosteroid therapy for critically ill patients with Middle East respiratory syndrome. Am J Respir Crit Care Med. 2018;197(6):757-767. Available at: https://www.ncbi.nlm.nih.gov/pubmed/29161116.
  6. Stockman LJ, Bellamy R, Garner P. SARS: systematic review of treatment effects. PLoS Med. 2006;3(9):e343. Available at: https://www.ncbi.nlm.nih.gov/pubmed/16968120.
  7. Rodrigo C, Leonardi-Bee J, Nguyen-Van-Tam J, Lim WS. Corticosteroids as adjunctive therapy in the treatment of influenza. Cochrane Database Syst Rev. 2016;3:CD010406. Available at: https://www.ncbi.nlm.nih.gov/pubmed/26950335.
  8. Horby P, Lim WS, Emberson J, et al. Effect of dexamethasone in hospitalized patients with COVID-19: preliminary report. medRxiv. 2020:[Preprint]. Available at: https://www.medrxiv.org/content/10.1101/2020.06.22.20137273v1.
  9. Kaiser UB, Mirmira RG, Stewart PM. Our response to COVID-19 as endocrinologists and diabetologists. J Clin Endocrinol Metab. 2020;105(5). Available at: https://www.ncbi.nlm.nih.gov/pubmed/32232480.
  10. Liggins GC, Howie RN. A controlled trial of antepartum glucocorticoid treatment for prevention of the respiratory distress syndrome in premature infants. Pediatrics. 1972;50(4):515-525. Available at: https://www.ncbi.nlm.nih.gov/pubmed/4561295.
  11. Gyamfi-Bannerman C, Thom EA, Blackwell SC, et al. Antenatal betamethasone for women at risk for late preterm delivery. N Engl J Med. 2016;374(14):1311-1320. Available at: https://www.ncbi.nlm.nih.gov/pubmed/26842679.
  12. Fedson DS, Opal SM, Rordam OM. Hiding in plain sight: an approach to treating patients with severe COVID-19 infection. mBio. 2020;11(2). Available at: https://www.ncbi.nlm.nih.gov/pubmed/32198163.
  13. Bancos S, Bernard MP, Topham DJ, Phipps RP. Ibuprofen and other widely used non-steroidal anti-inflammatory drugs inhibit antibody production in human cells. Cell Immunol. 2009;258(1):18-28. Available at: https://www.ncbi.nlm.nih.gov/pubmed/19345936.
  14. Food and Drug Administration. FDA advises patients on use of non-steroidal anti-inflammatory drugs (NSAIDs) for COVID-19. 2020. https://www.fda.gov/drugs/drug-safety-and-availability/fda-advises-patients-use-non-steroidal-anti-inflammatory-drugs-nsaids-covid-19. Accessed July 16, 2020.